| Prostate cancer (PCa) is the second leading cause of cancer-relateddeaths and the most commonly diagnosed cancer in elderly men in thewestern countries.With the population ageing and the the changing of lifestyle,the rate of diagnosis is increasing quickly in Asia,becoming a veryserious disease in older generations.Zinc is one of the essential trace element in human body.It has aconsiderable role on cell growth and differentiation,nucleic acid proteinmetabolism,gene expression,the regulation of both hormones and enzymaticactivity and the maintainence of biological membrane normal structure andfunction.The content of Zinc in normal prostate tissue is higher than that in anyother tissues in the human body, about 3 to 10 fold greater than others.Butthe content of Zinc in prostate cancer tissue is considerably lower than thatin normal prostate tissue.One of the main causes of death in prostate cancer patients is themetastasis of prostate tumors. The mechanism of metastasis is mostlybecause of the destruction of the extracellular matrix (ECM).Matrix metalloproteinases (MMPs) is clusters of proteases that containZinc.MMPs mainly participate in degrading tissues including bones.Gelatinase,MMP-2 and MMP-9 play a significant role in cancer growth andmetastasis.Matrix metalloproteinases (MMPs) is a family of structurally andfunctionally related Zinc-containing endopeptidases that are capable ofdegrading almost all of the components of the extracellular matrix (ECM).Under physiological and pathological conditions, MMPs play a significantrole in the efficient tissue turnover and remodeling. Specific MMPs areresponsible for the matrix degradation and remodeling. Maintenance of theequilibrium between deposition and degradation of the extracellular matrix isessential to the normal tissue development. Therefore, synthesis andbreakdown of the MMPs are tightly controlled by protein kinases whichmediate a host of other cellular processes. The MMPs are often induced byseveral agents, any uncontrolled expression of the MMPs can contribute tothe pathogenesis of many human diseases. This paper focuses on theregulation of the MMPs by the protein kinases at the level of geneexpression and their signaling pathways.Objective: To study the effect of Zinc on apoptosis and mmp-2 andmmp-9 activity in androgen independent prostate cancer cell lines (PC-3M).Method: To determine cell proliferation by MTT assay, to observe thecell morphology changes exposured by Zinc for 24 hour by phase-contrastmicroscope, to detect apoptosis by AO/EB assay, to detect cell cycle andapoptotic peak by flow cytometry, to observe DNA fragmentation by agarosegel electrophoresis,the level of Bcl-2 and Bax mRNA were measured byRT-PCR,the activity of MMP-2,-9 were dectected by zymography.Results:1).PC-3M cells proliferation rate is oberviously changed afterexposure to different levels of Zinc for 24 hour. Zinc(250μM) can inhibiteproliferation of PC-3M cells (P<0.01).2).The changes of PC-3M cells wereobserved by inverted microscope.Compared to the control cells, changes ofmorphological characteristics,including shrank and floated, refractiondecreased happened in the cells exposured to Zinc(250μM)for 24 hour.3).The confocal microscopy showed the changes of cells through AO/EBstaining. The cellular membrane was integrity but vacuolization of thecytoplasm, chromatin was flavo-green, nuclear condensed, nuclear sidecollection, caryolysis, nuclear fragmented .and apoptotic bodies.4).Theflow cytometry showed the hypodiploid peak in G0/G1 phase afterexposure to Zinc (250μM) for 24 hour.5).It has visible DNA fragmentationby AGE.6).The expression of Bcl-2 mRNA decreased the expression ofBax increased by RT-PCR.7).The activity of MMP-2,9 were inhibited byZinc(250μM) .Conclusion:Zinc can inhibit the proliferation of PC-3M cells andinduce apoptosis,the apoptotic mechanism possibly has a relationship withthe increasing of Bax lever and the decreasing of Bcl-2 lever .Zinc caninhibit the activity of MMP-2,9. |
